Metformin for the Treatment of Premature Pubarche in Girls

Overview[ - collapse ][ - ]

Purpose The primary objective of this study is to determine the safety and efficacy of metformin in lowering serum DHEAS levels in girls with premature pubarche and secondary, to observe changes in hormones associated with pubertal development including gonadotropins, sex steroids, insulin, adipocytokines, and growth factors.
ConditionPremature Pubarche
InterventionDrug: sugar pill
Drug: Metformin, glucophage
PhaseN/A
SponsorMilton S. Hershey Medical Center
Responsible PartyMilton S. Hershey Medical Center
ClinicalTrials.gov IdentifierNCT01316042
First ReceivedMarch 15, 2011
Last UpdatedJune 17, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateMarch 15, 2011
Last Updated DateJune 17, 2013
Start DateMay 2011
Estimated Primary Completion DateApril 2014
Current Primary Outcome MeasuresChange in serum DHEAS levels [Time Frame: 1 year] [Designated as safety issue: No]
Current Secondary Outcome Measuresprogression of puberty [Time Frame: 12 months] [Designated as safety issue: No]progression of puberty as determined by change in hormones associated with pubertal development

Descriptive Information[ + expand ][ + ]

Brief TitleMetformin for the Treatment of Premature Pubarche in Girls
Official TitleA Double Blind Randomized Controlled 12 Month Trial of Metformin for the Treatment of Premature Pubarche in Girls
Brief Summary
The primary objective of this study is to determine the safety and efficacy of metformin in
lowering serum DHEAS levels in girls with premature pubarche and secondary, to observe
changes in hormones associated with pubertal development including gonadotropins, sex
steroids, insulin, adipocytokines, and growth factors.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionPremature Pubarche
InterventionDrug: sugar pill
2 pills per day for 12 months
Drug: Metformin, glucophage
2 212.5mg pills/day for 12 months
Other Names:
metformin
Study Arm (s)
  • Placebo Comparator: sugar pill
    2 pills per day for 12 months
  • Active Comparator: Metformin
    2 212.5mg pill/day for 12 months

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment60
Estimated Completion DateApril 2014
Estimated Primary Completion DateDecember 2013
Eligibility Criteria
Inclusion Criteria:

1. Girls aged 4-10 with pubic hair prior to 8 years of age

2. Elevated DHEAS level above age normal levels

3. Informed consent from parents and assent from the girl

Exclusion Criteria:

1. Diagnosis of incomplete precocious puberty, peripheral precocious puberty, or
evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid, and gonadal
function other than premature secretion of adrenal androgens.

2. Chronic illness requiring treatment that may interfere with growth and development,
i.e. chronic steroid use, renal failure, etc.

3. 21-hydroxylase deficiency or other enzyme deficiency leading to the phenotype of
congenital adrenal hyperplasia. 21-hydroxylase deficiency will be excluded in all
patients by a fasting 17-hydroxyprogesterone (17-OHP) level < 2 ng/mL. In the
case of elevated fasting 17-OHP levels, an ACTH stimulation test will be performed. A
1-hour stimulated value > 10 ng/mL will be an exclusion 82. As 21 hydroxylase
deficiency is a congenital condition, any normal level in the past of
17-hydroxyprogesterone allows entry into this study.

4. Uncorrected thyroid disease (defined as TSH < 0.2 mIU/ML or > 5.5 mIU/mL). A normal
level within the last year is adequate for entry.

5. Type I or Type II diabetes (defined as a fasting serum glucose > 125mg/dL on two
occasions 83), or patients receiving anti-diabetic medications such as insulin,
thiazolidinediones, acarbose, or sulfonylureas; patients currently receiving
metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also
specifically excluded.

6. Liver disease defined as AST or ALT > 2 times normal or total bilirubin > 2.5 mg/dL.

7. Renal disease defined as BUN > 30 mg/dL or serum creatinine > 1.4 mg/dL.

8. Significant anemia (Hemoglobin < 10 mg/dL).

9. History of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.

10. Known heart disease (New York Heart Association Class II or higher).

11. Enrolled simultaneously into other investigative studies that require medications,
proscribe the study medications, or otherwise prevent compliance with the protocol.
Patients who anticipate taking longer than a one month break during the protocol
should not be enrolled.

12. Concomitant use other medications known to affect reproductive function or
metabolism. These medications include growth hormone, IGF-1, medroxyprogesterone
acetate, oral contraceptives, GnRH agonists and antagonists, anti-androgens,
gonadotropins, anti-obesity drugs, somatostatin, diazoxide, ACE inhibitors, and
calcium channel blockers. The washout period on all these medications will be three
months.

13. Suspected adrenal or ovarian tumor secreting androgens or other ectopic steroid
secreting tumor.

14. Suspected Cushing's syndrome.

15. Lactose intolerance (the placebo filler is lactose).

16. Known hypersensitivity to study medication, including ACTH and GnRH, or their
excipients.

17. Any concomitant medical condition that in the opinion of the investigator, may expose
a subject to unacceptable level of safety risk, or that affects subject compliance.

18. Subjects who anticipate having any surgery associated with restricted intake of
fluids or radiological studies with contrast dye during the study period.

19. Any concomitant medical condition that in the opinion of the investigator, may expose
a subject to unacceptable level of safety risk, or that affects subject compliance.
GenderFemale
Ages4 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01316042
Other Study ID Numbers35865
Has Data Monitoring CommitteeYes
Information Provided ByMilton S. Hershey Medical Center
Study SponsorMilton S. Hershey Medical Center
CollaboratorsNot Provided
Investigators Principal Investigator: Richard S Legro, MD Penn State Hershey Medical Center
Verification DateJune 2013

Locations[ + expand ][ + ]

Riley Hospital for Children, Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15224